Journal article
Using extracellular matrix derived from sugen-chronic hypoxia lung tissue to study pulmonary arterial hypertension
Frontiers in pharmacology, Vol.14, p.1192798
09/05/2023
DOI: 10.3389/fphar.2023.1192798
PMCID: PMC10507686
PMID: 37731734
Abstract
Pulmonary arterial hypertension has characteristic changes to the mechanical environment, extracellular matrix, and cellular proliferation. In order to develop a culture system to investigate extracellular matrix (ECM) compositional-dependent changes in pulmonary arterial hypertension, we decellularized and characterized protein and lipid profiles from healthy and Sugen-Chronic Hypoxia rat lungs. Significant changes in lipid profiles were observed in intact Sugen-Hypoxia lungs compared with healthy controls. Decellularized lung matrix retained lipids in measurable quantities in both healthy and Sugen-Chronic Hypoxia samples. Proteomics revealed significantly changed proteins associated with pulmonary arterial hypertension in the decellularized Sugen-Chronic Hypoxia lung ECM. We then investigated the potential role of healthy vs. Sugen-Chronic Hypoxia ECM with controlled substrate stiffness to determine if the ECM composition regulated endothelial cell morphology and phenotype. CD117+ rat lung endothelial cell clones were plated on the variable stiffness gels and cellular proliferation, morphology, and gene expression were quantified. Sugen-Chronic Hypoxia ECM on healthy stiffness gels produced significant changes in cellular gene expression levels of Bmp2, Col1α1, Col3α1 and Fn1. The signaling and cell morphology observed at low substrate stiffness suggests early changes to the ECM composition can initiate processes associated with disease progression. These data suggest that Sugen-Chronic Hypoxia ECM can be used to investigate cell-ECM interactions relevant to pulmonary arterial hypertension.
Details
- Title: Subtitle
- Using extracellular matrix derived from sugen-chronic hypoxia lung tissue to study pulmonary arterial hypertension
- Creators
- Patrick A. Link - Virginia Commonwealth UniversityLaszlo Farkas - The Ohio State University Wexner Medical CenterRebecca L. Heise - Virginia Commonwealth University
- Resource Type
- Journal article
- Publication Details
- Frontiers in pharmacology, Vol.14, p.1192798
- DOI
- 10.3389/fphar.2023.1192798
- PMID
- 37731734
- PMCID
- PMC10507686
- NLM abbreviation
- Front Pharmacol
- ISSN
- 1663-9812
- eISSN
- 1663-9812
- Publisher
- Frontiers Media S.A
- Alternative title
- Link et al
- Language
- English
- Date published
- 09/05/2023
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Craniofacial Anomalies Research Center
- Record Identifier
- 9984948041402771
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